In-depth structural characterization of the tetraspanin CD81

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

The BBSRC policy news website states that the bio-based economy "encompasses a wide range of activities that use bioscience-based research or processes to produce products, food, fuel or therapies. Across Europe the sector already represents a market worth over 1.5 trillion Euros and more than 22 million people are employed in the bioeconomy".

The outputs of this project will directly contribute to the bio-based economy through their potential for commercial application: CD81 has a well-established role in infection by various pathogens including influenza, human immunodeficiency virus, the malarial plasmodium parasite, human T-cell lymphotropic virus type 1 and hepatitis C virus; it has also been proposed to be a tumour promoter. CD81 is involved in essential physiological processes including cell-cell adhesion, cell proliferation, the immune response and fertilization. An understanding of how CD81 forms homomeric and heteromeric complexes will therefore impact on our knowledge of many different proteins with fundamental biological functions as well as those involved in cancers and infectious diseases.

The outcomes of the proposed research will be exploited according to the "Pathways to Impact" document that accompanies this proposal and is likely to benefit the following non-academic beneficiaries:

1. Scientists in pharmaceutical and biotechnology companies - this work seeks to define the first structure of the tetraspanin family. We will also establish the oligomeric status of the CD81 functional unit. This knowledge will enable new drug targets to be defined and, in the long term, facilitate the development of allosteric ligands that can enter drug development pipelines;

2. UK economic competitiveness - No complex of a viral attachment protein together with an integral membrane receptor has been characterized in atomic detail to date; the results from this proposal will lead to the first such structure. This will be possible because of the expertise developed in this project on forming, stabilizing and characterizing HCV-E2/CD81 complexes. Potential exists for molecules or vaccine candidates to be developed by UK companies based on the new structural and functional understanding of CD81 complexes that will result from this project. In the long term, this will allow companies to create new jobs;

3. Patients - in the longer term, access to new and improved therapies for important human infections will be of direct benefit for patients, thereby improving the quality of life across the lifespan;

4. The scientists of tomorrow & their families- The primary impact of this research will be enhanced structural and functional understanding of a membrane protein (the tetraspanin, CD81) of broad biological and medical importance. Starting with our first display in 2016 (11th-20th March), we will build an exhibit to engage the public. We will show how microbes are used as biotechnological tools to make medically-important proteins that can be developed as drug targets. In the long-term, the exhibit will be used as part of Aston's ongoing links with Thinktank (Birmingham's science museum) which is directly opposite the Aston campus;

5. The researcher co-investigator, Dr Michelle Clare, and the PGRA on this proposal - MC generated preliminary data for this proposal during her BBSRC iCASE-funded PhD project and has established the experimental systems that underpin it. MC's exceptional crystal data are highly likely to lead to a high-impact publication within the first 18 months of the project. Supported by the high-quality portfolio of work, training by the investigator team and publications arising from the proposed project, (i) MC will be in a strong position to transition to independence by securing a personal fellowship at the end of the project and (ii) the PGRA will develop his/her employability by gaining sought-after EM, crystallization and other high-level technical skills.